weakness . palpitations . paraesthesia . seizure .taste
altered .tinnitus . vision blurred
▶ Rare or very rare Hepatitis . severe cutaneous adverse
SIDE-EFFECTS, FURTHER INFORMATION Manufacturer
advises increasing dose according to response and
Serious skin reactions Serious skin reactions
(including Stevens-Johnson syndrome and acute
generalized exanthematous pustulosis) have been
reported—manufacturer advises discontinue at the first
l PREGNANCY Use with caution—toxicity in animal studies.
l BREAST FEEDING Avoid—no information available.
l HEPATIC IMPAIRMENT Manufacturer advises caution in
moderate impairment (risk of increased plasma
concentrations); avoid in severe impairment (no
4 mg once daily (preferably in the morning) for at least
7 days, then 4 mg twice daily for at least 4 weeks;
Manufacturer advises for modified-release preparations
in moderate impairment, initially 8 mg on alternate days
(preferably in the morning) for 7 days, then 8 mg once
daily for 4 weeks; maximum 16 mg daily.
l RENAL IMPAIRMENT Avoid if eGFR less than
l PATIENT AND CARER ADVICE Manufacturer recommends
that patients are warned of the signs of serious skin
reactions; they should be advised to stop taking
galantamine immediately and seek medical advice if
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Donepezil, galantamine, rivastigmine, and memantine for the
treatment of Alzheimer’s disease (updated June 2018)
The three acetylcholinesterase (AChE) inhibitors
donepezil, galantamine, and rivastigmine as
monotherapies are recommended as options for managing
mild to moderate Alzheimer’s disease under all of the
conditions specified below and in recommendation 1.5.5 of
the NICE guideline on dementia.
If prescribing an AChE inhibitor (donepezil,
galantamine, or rivastigmine), treatment should normally
be started with the drug with the lowest acquisition cost
(taking into account required daily dose and the price per
dose once shared care has started). However, an
alternative AChE inhibitor could be prescribed if it is
considered appropriate when taking into account adverse
event profile, expectations about adherence, medical
comorbidity, possibility of drug interactions and dosing
Healthcare professionals should not rely solely on
assessment scales to determine the severity of Alzheimer’s
disease when the patient has learning or other disabilities,
or other communication difficulties.
www.nice.org.uk/guidance/ta217
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: tablet
CAUTIONARY AND ADVISORY LABELS 3, 21
▶ Galantamine (Non-proprietary)
Galantamine (as Galantamine hydrobromide) 4 mg per
1 ml Galantamine 20mg/5ml oral solution sugar free sugar-free | 100 ml P £120.00 DT = £120.00
Galantamine (as Galantamine hydrobromide) 4 mg per
1 ml Galzemic 4mg/ml oral solution sugar-free | 100 ml P £90.00
▶ Reminyl (Shire Pharmaceuticals Ltd)
Galantamine (as Galantamine hydrobromide) 4 mg per
1 ml Reminyl 4mg/ml oral solution sugar-free | 100 ml P £120.00 DT = £120.00
CAUTIONARY AND ADVISORY LABELS 3, 21, 25
Galantamine (as Galantamine hydrobromide) 8 mg Acumor XL
8mg capsules | 28 capsule P £49.26 DT = £51.88
Galantamine (as Galantamine hydrobromide) 16 mg Acumor XL
16mg capsules | 28 capsule P £61.65 DT = £64.90
Galantamine (as Galantamine hydrobromide) 24 mg Acumor XL
24mg capsules | 28 capsule P £75.81 DT = £79.80
▶ Consion XL (Dr Reddy’s Laboratories (UK) Ltd)
Galantamine (as Galantamine hydrobromide) 8 mg Consion XL
8mg capsules | 28 capsule P £25.94 DT = £51.88
Galantamine (as Galantamine hydrobromide) 16 mg Consion XL
16mg capsules | 28 capsule P £32.45 DT = £64.90
Galantamine (as Galantamine hydrobromide) 24 mg Consion XL
24mg capsules | 28 capsule P £39.90 DT = £79.80
Galantamine (as Galantamine hydrobromide) 8 mg Elmino XL
8mg capsules | 28 capsule P £51.88 DT = £51.88
Galantamine (as Galantamine hydrobromide) 16 mg Elmino XL
16mg capsules | 28 capsule P £64.90 DT = £64.90
Galantamine (as Galantamine hydrobromide) 24 mg Elmino XL
24mg capsules | 28 capsule P £79.80 DT = £79.80
Galantamine (as Galantamine hydrobromide) 8 mg Gaalin 8mg
modified-release capsules | 28 capsule P £51.88 DT = £51.88
Galantamine (as Galantamine hydrobromide) 16 mg Gaalin 16mg
modified-release capsules | 28 capsule P £64.90 DT = £64.90
Galantamine (as Galantamine hydrobromide) 24 mg Gaalin 24mg
modified-release capsules | 28 capsule P £79.80 DT = £79.80
▶ Galantex XL (Creo Pharma Ltd)
Galantamine (as Galantamine hydrobromide) 8 mg Galzemic XL
8mg capsules | 28 capsule P £19.05 DT = £51.88
Galantamine (as Galantamine hydrobromide) 16 mg Galzemic XL
16mg capsules | 28 capsule P £23.84 DT = £64.90
Galantamine (as Galantamine hydrobromide) 24 mg Galzemic XL
24mg capsules | 28 capsule P £29.32 DT = £79.80
▶ Galsya XL (Consilient Health Ltd)
Galantamine (as Galantamine hydrobromide) 8 mg Galsya XL
8mg capsules | 28 capsule P £44.09 DT = £51.88
Galantamine (as Galantamine hydrobromide) 16 mg Galsya XL
16mg capsules | 28 capsule P £55.16 DT = £64.90
Galantamine (as Galantamine hydrobromide) 24 mg Galsya XL
24mg capsules | 28 capsule P £67.83 DT = £79.80
▶ Gatalin XL (Aspire Pharma Ltd)
Galantamine (as Galantamine hydrobromide) 8 mg Gatalin XL
8mg capsules | 28 capsule P £25.94 DT = £51.88
Galantamine (as Galantamine hydrobromide) 16 mg Gatalin XL
16mg capsules | 28 capsule P £32.45 DT = £64.90
Galantamine (as Galantamine hydrobromide) 24 mg Gatalin XL
24mg capsules | 28 capsule P £39.90 DT = £79.80
Galantamine (as Galantamine hydrobromide) 8 mg Gazylan XL
8mg capsules | 28 capsule P £19.04 DT = £51.88
Galantamine (as Galantamine hydrobromide) 16 mg Gazylan XL
16mg capsules | 28 capsule P £23.83 DT = £64.90
Galantamine (as Galantamine hydrobromide) 24 mg Gazylan XL
24mg capsules | 28 capsule P £29.31 DT = £79.80
▶ Lotprosin XL (Actavis UK Ltd)
Galantamine (as Galantamine hydrobromide) 8 mg Lotprosin XL
8mg capsules | 28 capsule P £51.88 DT = £51.88
Galantamine (as Galantamine hydrobromide) 16 mg Lotprosin XL
16mg capsules | 28 capsule P £64.90 DT = £64.90
Galantamine (as Galantamine hydrobromide) 24 mg Lotprosin XL
24mg capsules | 28 capsule P £79.80 DT = £79.80
▶ Luventa XL (Fontus Health Ltd)
Galantamine (as Galantamine hydrobromide) 8 mg Luventa XL
8mg capsules | 28 capsule P £25.42 DT = £51.88
Galantamine (as Galantamine hydrobromide) 16 mg Luventa XL
16mg capsules | 28 capsule P £31.80 DT = £64.90
Galantamine (as Galantamine hydrobromide) 24 mg Luventa XL
24mg capsules | 28 capsule P £39.10 DT = £79.80
▶ Reminyl XL (Shire Pharmaceuticals Ltd)
Galantamine (as Galantamine hydrobromide) 8 mg Reminyl XL
8mg capsules | 28 capsule P £51.88 DT = £51.88
Galantamine (as Galantamine hydrobromide) 16 mg Reminyl XL
16mg capsules | 28 capsule P £64.90 DT = £64.90
Galantamine (as Galantamine hydrobromide) 24 mg Reminyl XL
24mg capsules | 28 capsule P £79.80 DT = £79.80
CAUTIONARY AND ADVISORY LABELS 3, 21
▶ Galantamine (Non-proprietary)
Galantamine (as Galantamine hydrobromide) 8 mg Galantamine
8mg tablets | 56 tablet P £59.25–£64.90 DT = £61.13
Galantamine (as Galantamine hydrobromide) 12 mg Galantamine
12mg tablets | 56 tablet P £71.25–£79.80 DT = £74.10
l DRUG ACTION Rivastigmine is a reversible noncompetitive inhibitor of acetylcholinesterases.
Mild to moderate dementia in Alzheimer’s disease
▶ Adult: Initially 1.5 mg twice daily, increased in steps of
1.5 mg twice daily, dose to be increased at intervals of
at least 2 weeks according to response and tolerance;
usual dose 3–6 mg twice daily (max. per dose 6 mg
twice daily), if treatment interrupted for more than
several days, retitrate from 1.5 mg twice daily
▶ BY TRANSDERMAL APPLICATION USING PATCHES
▶ Adult: Apply 4.6 mg/24 hours daily for at least 4 weeks,
increased if tolerated to 9.5 mg/24 hours daily for a
further 6 months, then increased if necessary to
13.3 mg/24 hours daily, increase to 13.3 mg/24 hours
patch if well tolerated and cognitive deterioration or
functional decline demonstrated; use caution in
patients with body-weight less than 50 kg, if treatment
interrupted for more than 3 days, retitrate from
Mild to moderate dementia in Parkinson’s disease
▶ Adult: Initially 1.5 mg twice daily, increased in steps of
1.5 mg twice daily, dose to be increased at intervals of
at least 2 weeks according to response and tolerance;
usual dose 3–6 mg twice daily (max. per dose 6 mg
twice daily), if treatment interrupted for more than
several days, retitrate from 1.5 mg twice daily
DOSE EQUIVALENCE AND CONVERSION
▶ When switching from oral to transdermal therapy,
patients taking 3–6 mg by mouth daily should initially
switch to 4.6 mg/24 hours patch, then titrate as above.
Patients taking 9 mg by mouth daily should switch to
9.5 mg/24 hours patch if oral dose stable and well
tolerated; if oral dose not stable or well tolerated.
patients should switch to 4.6 mg/24 hours patch, then
titrate as above. Patients taking 12 mg by mouth daily
should switch to 9.5 mg/24 hours patch. The first patch
should be applied on the day following the last oral
l CAUTIONS Bladder outflow obstruction . conduction
abnormalities . duodenal ulcers . gastric ulcers . history of
administration errors . sick sinus syndrome . susceptibility
l INTERACTIONS → Appendix 1: anticholinesterases,
reactions . syncope .tremor. urinary incontinence . urinary
tract infection . vomiting . weight decreased
▶ Uncommon Aggression . atrioventricular block
▶ Rare or very rare Pancreatitis . seizure
▶ Frequency not known Hepatitis
▶ With transdermal use Gastric ulcer
▶ With oral use Angina pectoris . gastrointestinal disorders . gastrointestinal haemorrhage
▶ With transdermal use Hallucination . nightmare
SIDE-EFFECTS, FURTHER INFORMATION Dose should be
started low and increased according to response if
Treatment should be interrupted if dehydration
resulting from prolonged vomiting or diarrhoea occurs and
withheld until resolution—retitrate dose if necessary.
Transdermal administration is less likely to cause
l HEPATIC IMPAIRMENT Manufacturer advises caution (risk
of increased exposure; no information available in severe
Dose adjustments Manufacturer advises cautious dose
titration according to individual tolerability.
Dose adjustments Titrate according to individual
l MONITORING REQUIREMENTS Monitor body-weight.
l DIRECTIONS FOR ADMINISTRATION
▶ With transdermal use Apply patches to clean, dry, non-hairy,
non-irritated skin on back, upper arm, or chest, removing
after 24 hours and siting a replacement patch on a
different area (avoid using the same area for 14 days).
EXELON ® PATCHES Advise patients and carers of patch
administration instructions, particularly to remove the
previous day’s patch before applying the new patch—
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Donepezil, galantamine, rivastigmine, and memantine for the
treatment of Alzheimer’s disease (updated June 2018)
The three acetylcholinesterase (AChE) inhibitors
donepezil, galantamine, and rivastigmine as
monotherapies are recommended as options for managing
mild to moderate Alzheimer’s disease under all of the
conditions specified below and in recommendation 1.5.5 of
the NICE guideline on dementia.
If prescribing an AChE inhibitor (donepezil,
galantamine, or rivastigmine), treatment should normally
be started with the drug with the lowest acquisition cost
(taking into account required daily dose and the price per
dose once shared care has started). However, an
alternative AChE inhibitor could be prescribed if it is
considered appropriate when taking into account adverse
event profile, expectations about adherence, medical
comorbidity, possibility of drug interactions and dosing
Healthcare professionals should not rely solely on
assessment scales to determine the severity of Alzheimer’s
disease when the patient has learning or other disabilities,
or other communication difficulties.
www.nice.org.uk/guidance/ta217
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (October
2007) that Exelon ® patches should be restricted for use in
patients with moderately severe Alzheimer’s disease under
the conditions of the NICE guidance (September 2007) and
when a transdermal patch is an appropriate choice of
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 21
▶ Rivastigmine (Non-proprietary)
Rivastigmine (as Rivastigmine hydrogen tartrate) 2 mg per
1 ml Rivastigmine 2mg/ml oral solution sugar free sugar-free | 120 ml P £96.82 DT = £96.82
CAUTIONARY AND ADVISORY LABELS 21, 25
▶ Rivastigmine (Non-proprietary)
Rivastigmine (as Rivastigmine hydrogen tartrate)
1.5 mg Rivastigmine 1.5mg capsules | 28 capsule P £28.26 DT =
Rivastigmine (as Rivastigmine hydrogen tartrate)
3 mg Rivastigmine 3mg capsules | 28 capsule P £33.25 DT =
£3.16 | 56 capsule P £5.22–£6.32
Rivastigmine (as Rivastigmine hydrogen tartrate)
4.5 mg Rivastigmine 4.5mg capsules | 28 capsule P £33.25 DT =
£23.53 | 56 capsule P £28.66–£47.06
Rivastigmine (as Rivastigmine hydrogen tartrate)
6 mg Rivastigmine 6mg capsules | 28 capsule P £29.17 DT =
£29.17 | 56 capsule P £31.78–£58.34
▶ Nimvastid (Consilient Health Ltd)
Rivastigmine (as Rivastigmine hydrogen tartrate)
1.5 mg Nimvastid 1.5mg capsules | 28 capsule P £28.26 DT =
Rivastigmine (as Rivastigmine hydrogen tartrate) 3 mg Nimvastid
3mg capsules | 28 capsule P £28.26 DT = £3.16
Rivastigmine (as Rivastigmine hydrogen tartrate)
4.5 mg Nimvastid 4.5mg capsules | 28 capsule P £28.26 DT =
Rivastigmine (as Rivastigmine hydrogen tartrate)
6 mg Nimvastid 6mg capsules | 28 capsule P £28.26 DT = £29.17
Rivastigmine 4.6 mg per 24 hour Almuriva 4.6mg/24hours
transdermal patches | 30 patch P £77.97 DT = £77.97
Rivastigmine 9.5 mg per 24 hour Almuriva 9.5mg/24hours
transdermal patches | 30 patch P £77.97 DT = £19.97
▶ Alzest (Dr Reddy’s Laboratories (UK) Ltd)
Rivastigmine 4.6 mg per 24 hour Alzest 4.6mg/24hours
transdermal patches | 30 patch P £35.10 DT = £77.97
Rivastigmine 9.5 mg per 24 hour Alzest 9.5mg/24hours
transdermal patches | 30 patch P £19.97 DT = £19.97
▶ Exelon (Novartis Pharmaceuticals UK Ltd)
Rivastigmine 4.6 mg per 24 hour Exelon 4.6mg/24hours
transdermal patches | 30 patch P £77.97 DT = £77.97
Rivastigmine 9.5 mg per 24 hour Exelon 9.5mg/24hours
transdermal patches | 30 patch P £77.97 DT = £19.97
Rivastigmine 13.3 mg per 24 hour Exelon 13.3mg/24hours
transdermal patches | 30 patch P £77.97 DT = £77.97
Rivastigmine 13.3 mg per 24 hour Erastig 13.3mg/24hours
transdermal patches | 30 patch P £73.90 DT = £77.97
Rivastigmine 4.6 mg per 24 hour Voleze 4.6mg/24hours
transdermal patches | 30 patch P £77.97 DT = £77.97
Rivastigmine 13.3 mg per 24 hour Voleze 13.3mg/24hours
transdermal patches | 30 patch P £77.97 DT = £77.97
DOPAMINERGIC DRUGS › NMDA RECEPTOR
Memantine hydrochloride 05-Aug-2018
l DRUG ACTION Memantine is a glutamate receptor
Moderate to severe dementia in Alzheimer’s disease
▶ Adult: Initially 5 mg once daily, then increased in steps
of 5 mg every week; usual maintenance 20 mg daily;
l CAUTIONS Epilepsy . history of convulsions .risk factors
l INTERACTIONS → Appendix 1: memantine
▶ Frequency not known Hepatitis . pancreatitis . psychotic
l PREGNANCY Manufacturer advises avoid unless
essential—no information available.
l BREAST FEEDING Manufacturer advises avoid—no
l HEPATIC IMPAIRMENT Manufacturer advises avoid in
severe impairment—no information available.
l RENAL IMPAIRMENT Avoid if eGFR less than
Dose adjustments Reduce dose to 10 mg daily if eGFR
, if well tolerated after at least
7 days dose can be increased in steps to 20 mg daily;
reduce dose to 10 mg daily if eGFR
l DIRECTIONS FOR ADMINISTRATION For oral solution,
manufacturer advises solution should be dosed onto a
spoon or into a glass of water. For soluble tablets,
manufacturer advises drink resulting solution immediately
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Donepezil, galantamine, rivastigmine, and memantine for the
treatment of Alzheimer’s disease (updated June 2018)
Memantine monotherapy is recommended as an option for
managing Alzheimer’s disease for people with:
. moderate Alzheimer’s disease who are intolerant of or
have a contra-indication to AChE inhibitors, or
Treatment should be under the conditions specified in
recommendation 1.5.5 in the NICE guideline on dementia.
Healthcare professionals should not rely solely on
assessment scales to determine the severity of Alzheimer’s
disease when the patient has learning or other disabilities,
or other communication difficulties.
www.nice.org.uk/guidance/ta217
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 13
▶ Alzhok (Glenmark Pharmaceuticals Europe Ltd)
Alzhok soluble tablets treatment initiation pack sugar-free | 28 tablet P £40.97
Memantine hydrochloride 5 mg Alzhok 5mg soluble tablets sugarfree | 7 tablet P s
Memantine hydrochloride 10 mg Alzhok 10mg soluble tablets
sugar-free | 28 tablet P £29.09 DT = £29.09
Memantine hydrochloride 15 mg Alzhok 15mg soluble tablets
Memantine hydrochloride 20 mg Alzhok 20mg soluble tablets
sugar-free | 28 tablet P £58.18 DT = £58.18
▶ Memantine hydrochloride (Non-proprietary)
Memantine 5mg/10mg/15mg/20mg tablets treatment initiation pack
| 28 tablet P £43.13 DT = £43.13
Memantine hydrochloride 5 mg Memantine 5mg tablets | 7 tablet P s
Memantine hydrochloride 15 mg Memantine 15mg tablets |
Memantine hydrochloride 20 mg Memantine 20mg tablets | 28 tablet P £69.01 DT = £1.51
Ebixa tablets treatment initiation pack | 28 tablet P £43.13 DT =
Memantine hydrochloride 5 mg Ebixa 5mg tablets |
Memantine hydrochloride 10 mg Ebixa 10mg tablets | 28 tablet P £34.50 DT = £1.19
Memantine hydrochloride 15 mg Ebixa 15mg tablets | 7 tablet P s
Memantine hydrochloride 20 mg Ebixa 20mg tablets | 28 tablet P £69.01 DT = £1.51
▶ Marixino (Consilient Health Ltd)
Memantine hydrochloride 10 mg Marixino 10mg tablets |
Memantine hydrochloride 20 mg Marixino 20mg tablets | 28 tablet P £58.65 DT = £1.51
Nemdatine tablets treatment initiation pack | 28 tablet P £43.12
Memantine hydrochloride 5 mg Nemdatine 5mg tablets |
Memantine hydrochloride 15 mg Nemdatine 15mg tablets | 7 tablet P s
Memantine hydrochloride 20 mg Nemdatine 20mg tablets | 28 tablet P £69.01 DT = £1.51
▶ Memantine hydrochloride (Non-proprietary)
Memantine hydrochloride 10 mg per 1 ml Memantine 10mg/ml
oral solution sugar free sugar-free | 50 ml P £61.61 DT = £54.99
sugar-free | 100 ml P £97.98–£123.23
Memantine hydrochloride 10 mg per 1 ml Ebixa 5mg/0.5ml pump
actuation oral solution sugar-free | 50 ml P £61.61 DT = £54.99
EXCIPIENTS: May contain Aspartame
▶ Valios (Dr Reddy’s Laboratories (UK) Ltd)
Valios 5mg/10mg/15mg/20mg orodispersible tablets initiation pack
sugar-free | 28 tablet P £31.24
Memantine hydrochloride 5 mg Valios 5mg orodispersible tablets
sugar free sugar-free | 7 tablet P s
Memantine hydrochloride 10 mg Valios 10mg orodispersible
tablets sugar free sugar-free | 28 tablet P £24.99 DT = £24.99
Memantine hydrochloride 15 mg Valios 15mg orodispersible tablets
sugar free sugar-free | 7 tablet P s
Memantine hydrochloride 20 mg Valios 20mg orodispersible
tablets sugar free sugar-free | 28 tablet P £49.98 DT = £49.98
The object of treatment is to prevent the occurrence of
seizures by maintaining an effective dose of one or more
antiepileptic drugs. Careful adjustment of doses is necessary,
starting with low doses and increasing gradually until
seizures are controlled or there are significant adverse
When choosing an antiepileptic drug, the presenting
epilepsy syndrome should first be considered. If the
syndrome is not clear, the seizure type should determine the
choice of treatment. Concomitant medication, co-morbidity,
age, and sex should also be taken into account.
encourage adherence with the prescribed regimen. Most
antiepileptics, when used in the usual dosage, can be given
BNF 78 Epilepsy and other seizure disorders 305
twice daily. Lamotrigine p. 318, perampanel p. 322,
phenobarbital p. 335, and phenytoin p. 323, which have long
half-lives, can be given once daily at bedtime. However, with
large doses, some antiepileptics may need to be given more
frequently to avoid adverse effects associated with high peak
When monotherapy with a first-line antiepileptic drug has
failed, monotherapy with a second drug should be tried; the
diagnosis should be checked before starting an alternative
drug if the first drug showed lack of efficacy. The change
from one antiepileptic drug to another should be cautious,
slowly withdrawing the first drug only when the new regimen
has been established. Combination therapy with two or more
antiepileptic drugs may be necessary, but the concurrent use
of antiepileptic drugs increases the risk of adverse effects
and drug interactions. If combination therapy does not bring
about worthwhile benefits, revert to the regimen
(monotherapy or combination therapy) that provided the
best balance between tolerability and efficacy. A single
antiepileptic drug should be prescribed wherever possible.
MHRA/CHM advice: Antiepileptic drugs: updated advice on
switching between different manufacturers’ products
The CHM has reviewed spontaneous adverse reactions
received by the MHRA and publications that reported
potential harm arising from switching of antiepileptic drugs
in patients previously stabilised on a branded product to a
generic. The CHM concluded that reports of loss of seizure
control and/or worsening of side-effects around the time of
switching between products could be explained as chance
associations, but that a causal role of switching could not be
ruled out in all cases. The following guidance has been
. Different antiepileptic drugs vary considerably in their
characteristics, which influences the risk of whether
switching between different manufacturers’ products of a
particular drug may cause adverse effects or loss of seizure
whether it is necessary to maintain continuity of supply of
a specific manufacturer’s product. These categories are
. If it is felt desirable for a patient to be maintained on a
specific manufacturer’s product this should be prescribed
either by specifying a brand name, or by using the generic
drug name and name of the manufacturer (otherwise
known as the Marketing Authorisation Holder);
. This advice relates only to antiepileptic drug use for
treatment of epilepsy; it does not apply to their use in
other indications (e.g. mood stabilisation, neuropathic
. Please report on a Yellow Card any suspected adverse
reactions to antiepileptic drugs;
. Dispensing pharmacists should ensure the continuity of
supply of a particular product when the prescription
specifies it. If the prescribed product is unavailable, it may
be necessary to dispense a product from a different
manufacturer to maintain continuity of treatment of that
antiepileptic drug. Such cases should be discussed and
agreed with both the prescriber and patient (or carer);
. Usual dispensing practice can be followed when a specific
Carbamazepine p. 311, phenobarbital, phenytoin,
primidone p. 336. For these drugs, doctors are advised to
ensure that their patient is maintained on a specific
Clobazam p. 336, clonazepam p. 337, eslicarbazepine
acetate p. 313, lamotrigine, oxcarbazepine p. 321,
perampanel, rufinamide p. 326, topiramate p. 331,
valproate, zonisamide p. 334. For these drugs, the need for
continued supply of a particular manufacturer’s product
should be based on clinical judgement and consultation with
the patient and/or carer taking into account factors such as
seizure frequency, treatment history, and potential
implications to the patient of having a breakthrough seizure.
Non-clinical factors as for Category 3 drugs should also be
Brivaracetam p. 310, ethosuximide p. 314, gabapentin
p. 315, lacosamide p. 317, levetiracetam p. 320,
pregabalin p. 324, tiagabine p. 331, vigabatrin p. 333.
For these drugs, it is usually unnecessary to ensure that
patients are maintained on a specific manufacturer’s product
as therapeutic equivalence can be assumed, however, other
factors are important when considering whether switching is
appropriate. Differences between alternative products (e.g.
product name, packaging, appearance, and taste) may be
perceived negatively by patients and/or carers, and may lead
to dissatisfaction, anxiety, confusion, dosing errors, and
reduced adherence. In addition, difficulties for patients with
co-morbid autism, mental health problems, or learning
disability should also be considered.
Antiepileptic hypersensitivity syndrome
Antiepileptic hypersensitivity syndrome is a rare but
potentially fatal syndrome associated with some
antiepileptic drugs (carbamazepine, lacosamide,
lamotrigine, oxcarbazepine, phenobarbital, phenytoin,
primidone, and rufinamide); rarely cross-sensitivity occurs
between some of these antiepileptic drugs. Some other
antiepileptics (eslicarbazepine, stiripentol, and
zonisamide) have a theoretical risk. The symptoms usually
start between 1 and 8 weeks of exposure; fever, rash, and
lymphadenopathy are most commonly seen. Other systemic
signs include liver dysfunction, haematological, renal, and
pulmonary abnormalities, vasculitis, and multi-organ
failure. If signs or symptoms of hypersensitivity syndrome
occur, the drug should be withdrawn immediately, the
patient must not be re-exposed, and expert advice should be
Risk of suicidal thoughts and behaviour
The MHRA has advised (August 2008) that all antiepileptic
drugs are associated with a small increased risk of suicidal
thoughts and behaviour. Symptoms may occur as early as
one week after starting treatment. Patients should be
advised to seek medical advice if they develop any mood
changes, distressing thoughts, or feelings about suicide or
harming themselves, and should be referred for appropriate
Interactions between antiepileptics are complex and may
increase toxicity without a corresponding increase in
antiepileptic effect. Interactions are usually caused by
hepatic enzyme induction or inhibition; displacement from
protein binding sites is not usually a problem. These
interactions are highly variable and unpredictable.
Antiepileptic drugs should be withdrawn under specialist
supervision. Avoid abrupt withdrawal, particularly of
barbiturates and benzodiazepines, because this can
precipitate severe rebound seizures. Reduction in dosage
should be gradual and, in the case of barbiturates,
withdrawal of the drug may take months.
The decision to withdraw antiepileptic drugs from a
seizure-free patient, and its timing, is often difficult and
depends on individual circumstances. Even in patients who
have been seizure-free for several years, there is a significant
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